The overall objective of this work is to determine whether the biochemical basis of the pathogenesis of the secondary sequelae of diabetes mellitus is a function of the nonenzymatic glycosylation of body proteins. For the past several years we have shown studying the glycosylation of hemoglobin a model reaction from which we have developed this concept. During the past year we have extended our studies to the ocular lens and have found a similar nonenzymatic glycosylation that occurs with these proteins. The glycosylation imparts an increased susceptibility to sulfhydryl oxidation and the formation of high molecular weight aggregates which we believe are responsible for cataract formation in the hyperglycemic environment. During the next year we intend to measure the amount of glycosylated lysine residues found in normal and cataractous lenses of human patients. It is further proposed to look for nonenzymatic glycosylation of other important body proteins that have undergone pathological changes as a result of the diabetic state. In particular we intend to look at basement membrane of kidney and the myelin of peripheral nerves. The amount of the glycosylated lysine will be determined with a new method which we have developed in our studies on lens protein.